Does adeno-associated virus lead to clinical disease in the immunosuppressed?

Mindy Miner

Adeno-associated virus (AAV) is a paravirus that has been considered an attractive candidate vaccine vector (or “delivery system”) due to its presumed nonpathogenicity and specific integration into the host’s DNA. One caveat to using AAV as a vaccine vector is the effect on persons who have suppressed immune systems, such as hematopoietic cell transplant (HCT) recipients or those with AIDS. The epidemiology of AAV in these immunosuppressed populations is largely unknown, and as it progresses in development as a vaccine vector it is crucial to understand possible adverse clinical outcomes.

To help define clinical disease correlations of HCT recipients with AAV viremia, Dr. Judson Heugal, with VIDD member Michael Boeckh, VIDD affiliate staff scientist Meei-Li Huang, VIDD associate member David Fredricks, VIDD affiliate staff scientist Jane Kuypers and Center President and Director Lawrence Corey, developed a sensitive assay for detection of the virus in human tissue samples and used this technique to analyze viremia in weekly blood plasma samples from 145 HCT recipients. This assay, real-time polymerase chain reaction (RT-PCR), is a quantitative, highly specific and sensitive molecular technique that can detect as few as 23 viral copies per milliliter of human plasma. The authors found low level, transient AAV viremia in 4 (2.8%) of the 145 subjects, and two of the four died in close proximity to virus detection. No other clinical findings were substantial. This study showed that while transient AAV viremia can be detected in HCT recipients, the incidence is low and does not appear to correlate with any specific disease.